Questioning the Predictive Role of Carotid Intima–media Thickness

Carotid IMT as Surrogate End Point: Is There Evidence to Support this Role?

The measurement of IMT stimulated the idea of an 'atherosclerosis window' useful to monitor the efficacy of cardiovascular therapy. Indeed, several studies assessing the relationship between antihypertensive and lipid-lowering therapy with progression in carotid IMT were published.^[10–14] In particular, they were collected in two meta-analyses showing a slight but significant association of slow progression of carotid IMT associated with blood pressure reduction^[18] and with lipid-lowering therapy, respectively.^[19] From this point, it was quite natural to think of carotid IMT as an individual imaging tool, useful to track the progression of atherosclerosis. However, no study has ever been designed and powered to demonstrate such a relationship. Carotid IMT prognostic value has always relied on its relationship with other proven surrogate end points and never with cardiovascular events, as described above. The only study that was often quoted to demonstrate a putative relationship between IMT changes and cardiovascular risk was the study by Espeland et al.^[20] However, it should be stated that, technically, the Espeland et al. study consisted of the addition of change in carotid IMT as a covariate in a regression model of a meta-analysis of some statin trials. In particular, they demonstrated that the change in carotid IMT raised the summary odds ratio of developing a cardiovascular event on statin therapy from 0.48 to 0.64. In addition, they included few studies and focused only on those that directly compared statin therapy to placebo. Therefore, that was not a meta-analysis made on purpose to check if changes in IMT predict cardiovascular events. Thus, it does not appear appropriate to quote that study as a clear evidence of a significant relationship between change in carotid IMT and cardiovascular risk.

In view of the lacking evidence clearly describing relationship changes in carotid IMT and modification of cardiovascular prognosis and in order to achieve a number of subjects adequate to power a prognostic analysis, we conducted a meta-analysis examining the existing published literature investigating the change in carotid IMT and reporting cardiovascular events.^[21] We found that IMT changes; such as regression or progression, did not correlate with the occurrence of major cardiovascular events (Figure 2). This observation held true when the relationship was separately assessed for different categories of drugs (lipid lowering, antihypertensive, oral antidiabetic and antioxidant agents), when it was separately assessed in subjects with and without previous cardiovascular disease and also when several common effect modifiers were introduced in the analytic statistical model. Interestingly, at variance, low cholesterol lipoprotein levels modification predicted the risk of a cardiovascular event.^[21] Similarly, Goldberger et al. arrived at the same conclusions by analyzing the role of carotid IMT modification in predicting the risk of myocardial infarction.^[22] The observations of these meta-analyses should be interpreted cautiously, since their results are based on published articles and not on individual patient data. More properly, they should be treated as hypothesis generating. Furthermore, it can be argued that these meta-analyses included studies whose follow-up was not long. However, just recently, the results regarding a cohort of more then 6000 patients followed for 10 years has been published (Tromso study), confirming a disappointing prognostic role of increase in carotid IMT in comparison with carotid plaque area.^[23] Thus, despite the certain role of carotid IMT when taken as a baseline value to classify the cardiovascular risk of a patient, there is much less evidence for its role as an atherosclerosis follow-up tool.

(Enlarge Image)

Figure 2.

Meta-regression analysis between δ mean and maximum intima–media thickness.
(A & B) Coronary heart disease events and (C & D) cerebrovascular events. The log of ORs is reported on the y-axis, and the covariate is reported on the x-axis. Bubble size for each study is proportional to the inverse of the variance.
CBV: Cerebrovascular; CHD: Coronary heart disease; IMT: Intima–media thickness; max: Maximum; OR: Odds ratio.

Future Cardiol. 2011;7(5):651-656. © 2011 Future Medicine Ltd.

Cite this: Questioning the Predictive Role of Carotid Intima–media Thickness - Medscape - Sep 01, 2011.